Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Int J Mol Med. 2013 Nov;32(5):1001-10. doi: 10.3892/ijmm.2013.1481. Epub 2013 Sep 4.
Duhuo Jisheng Decoction (DHJSD), a well known traditional Chinese folk medicine, is used for eliminating stagnation, removing blood stasis, promoting blood circulation and alleviating pain; it is commonly used for the treatment of various diseases, including osteoarthritis (OA). However, the molecular mechanisms behind the therapeutic effects of OA remain unclear. In the present study, the effects of DHJSD on the morphology of articular cartilage and the G1/S cell cycle progression in chondrocytes, as well as the underlying mechanisms, were investigated. A total of 27 two‑month‑old male Sprague Dawley rats were randomly divided into 3 groups: the control group (no papain-induced OA; received an equivalent amount of saline only), the model group (papain-induced OA; received an equivalent amount of saline only) and the DHJSD group [papain-induced OA; received a clinical oral dose of DHJSD (9.3 g/kg/day)]. After 8 consecutive weeks of treatment, the morphological changes in articular cartilage were observed under an optical microscope and by transmission electron microscopy (TEM) and the mRNA and protein expression levels of cyclin D1, CDK4, CDK6, retinoblastoma protein (Rb) and p16 were measured by RT‑PCR and immunohistochemistry, respectively. Treatment with DHJSD significantly improved the arrangement of collagen fibers in the articular cartilage, as well as its structure and reduced cell degeneration compared with the model group. The mRNA and protein expression levels of cyclin D1, CDK4, CDK6 and Rb in the DHJSD‑treated group were significantly increased compared with those in the model group, whereas p16 expression was significantly downregulated. Taken together, these results indicate that DHJSD treatment promotes chondrocyte proliferation by promoting the G1/S checkpoint transition in the cell cycle and by upregulating the expression of cyclin D1, CDK4, CDK6 and Rb and downregulating the expression of p16 and this may, in part, explain its clinical efficacy in the treatment of osteoarthritis.
独活寄生汤（DHJSD）是一种著名的中药方剂，用于祛瘀、活血、止痛，常用于治疗各种疾病，包括骨关节炎（OA）。然而，OA 治疗效果的分子机制尚不清楚。本研究旨在探讨 DHJSD 对软骨形态和软骨细胞 G1/S 细胞周期进程的影响及其潜在机制。将 27 只 2 月龄雄性 Sprague Dawley 大鼠随机分为 3 组：对照组（未用木瓜蛋白酶诱导 OA，仅给予等量生理盐水）、模型组（用木瓜蛋白酶诱导 OA，仅给予等量生理盐水）和 DHJSD 组[用木瓜蛋白酶诱导 OA，给予临床口服剂量的 DHJSD（9.3 g/kg/天）]。连续治疗 8 周后，光学显微镜和透射电镜（TEM）观察关节软骨的形态变化，逆转录聚合酶链反应（RT-PCR）和免疫组织化学法分别检测细胞周期蛋白 D1、CDK4、CDK6、视网膜母细胞瘤蛋白（Rb）和 p16 的 mRNA 和蛋白表达水平。与模型组相比，DHJSD 治疗组关节软骨胶原纤维排列、结构及细胞退变明显改善。DHJSD 组细胞周期蛋白 D1、CDK4、CDK6 和 Rb 的 mRNA 和蛋白表达水平明显高于模型组，而 p16 表达明显下调。综上所述，DHJSD 治疗通过促进细胞周期 G1/S 检查点转换和上调 cyclin D1、CDK4、CDK6 和 Rb 的表达及下调 p16 的表达促进软骨细胞增殖，这可能部分解释了其治疗 OA 的临床疗效。
